IP Library › Patent Application 16731973

Patent Application

App. No. 16/731,973

METHODS OF TREATING CANCERS USING ANTI-GPRC5D ANTIBODIES

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Patent No.: US None
App. No.: 16/731,973

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Abstract

The presently disclosed subject matter provides antibodies that bind to GPRC5D and methods of using the same.

Claims (132)

1 . A method of treating a cancer in a subject, the method comprising administering to the subject an effective amount of an anti-G-protein coupled receptor family C group 5 member D (GPRC5D) antibody or an antigen-binding fragment thereof wherein the antibody or antigen-binding fragment thereof comprises:

(i) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:130, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:131, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:132; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:133, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:134, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:135;

(ii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:142, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:143, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:144; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:145, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:146, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:147;

(iii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:154, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:155, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:156; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:157, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:158, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:159;

(iv) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:160, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:161, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:162; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:163, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:164, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:165;

(v) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:166, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:167, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:168; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:169, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:170, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:171;

(vi) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:172, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:173, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:174; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:175, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:176, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:177;

(vii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:178, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:179, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:180; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:181, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:182, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:183;

(viii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:184, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:185, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:186; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:187, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:188, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:189;

(ix) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:190, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:191, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:192; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:193, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:194, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:195;

(x) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:196, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:197, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:198; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:199, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:200, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:201;

(xi) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:202, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:203, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:204; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:205, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:206, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:207;

(xii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:208, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:209, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:210; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:211, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:212, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:213;

(xiii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:214, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:215, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:216; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:217, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:218, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:219;

(xiv) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:220, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:221, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:222; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:223, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:224, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:225;

(xv) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:226, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:227, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:228; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:229, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:230, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:231;

(xvi) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:232, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:233, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:234; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:235, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:236, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:237;

(xvii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:238, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:239, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:240; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:241, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:242, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:243;

(xviii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:244, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:245, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:246; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:247, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:248, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:249;

(xix) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:250, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:251, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:252; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:253, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:254, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:255;

(xx) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:256, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:257, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:258; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:259, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:260, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:261;

(xxi) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:262, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:263, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:264; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:265, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:266, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:267;

(xxii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:292, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:293, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:294; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:295, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:296, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:297;

(xxiii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:303, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:304, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:305; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:306, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:307, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:308;

(xxiv) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:316, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:317, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:318; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:319, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:320, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:321;

(xxv) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:328, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:329, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:330; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:331, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:332, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:333;

(xxvi) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:340, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:341, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:342; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:343, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:344, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:345; or

(xxvii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:352, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:353, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:354; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:355, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:356, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:357.

2 . A method of treating a cancer in a subject, the method comprising administering to the subject an effective amount of an anti-G-protein coupled receptor family C group 5 member D (GPRC5D) antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises:

(a) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:5, SEQ ID NO:13, SEQ ID NO:21, SEQ ID NO:25, SEQ ID NO:29, SEQ ID NO:33, SEQ ID NO:37, SEQ ID NO:41, SEQ ID NO:45, SEQ ID NO:49, SEQ ID NO:53, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:65, SEQ ID NO:69, SEQ ID NO:73, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:85, SEQ ID NO:89, SEQ ID NO:93, SEQ ID NO:298, SEQ ID NO:310, SEQ ID NO:322, SEQ ID NO:334, SEQ ID NO:346, or SEQ ID NO:358; and

(b) a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:6, SEQ ID NO:14, SEQ ID NO:22, SEQ ID NO:26, SEQ ID NO:30, SEQ ID NO:34, SEQ ID NO:38, SEQ ID NO:42, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:54, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:66, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:86, SEQ ID NO:90, SEQ ID NO:94, SEQ ID NO:299, SEQ ID NO:311, SEQ ID NO:323, SEQ ID NO:335, SEQ ID NO:347, or SEQ ID NO:359.

3 . The method of claim 2 , wherein the heavy chain variable region and the light chain variable region are selected from the group consisting of:

(i) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:5, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:6;

(ii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:13, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:14;

(iii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:21, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:22;

(iv) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:25, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:26;

(v) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:29, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:30;

(vi) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:33, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:34;

(vii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:37, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:38;

(viii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:41, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:42;

(ix) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:45, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:46;

(x) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:49, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:50;

(xi) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:53, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:54;

(xii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:57, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:58;

(xiii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:61, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:62;

(xiv) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:65, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:66;

(xv) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:69, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:70;

(xvi) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:73, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:74;

(xvii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:77, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:78;

(xviii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:81, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:82;

(xix) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:85, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:86;

(xx) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:89, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:90;

(xxi) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:93, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:94;

(xxii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:298, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:299;

(xxiii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:310, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:311;

(xxix) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:322, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:323;

(xxv) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:334, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:335;

(xxvi) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:346, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:347; and

(xxvii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:358, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:359.

4 . The method of claim 1 , wherein the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:220, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:221, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:222; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:223, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:224, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:225.

5 . The method of claim 1 , wherein the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:226, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:227, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:228; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:229, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:230, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:231.

6 . The method of claim 1 , wherein:

(a) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:5, SEQ ID NO:13, SEQ ID NO:21, SEQ ID NO:25, SEQ ID NO:29, SEQ ID NO:33, SEQ ID NO:37, SEQ ID NO:41, SEQ ID NO:45, SEQ ID NO:49, SEQ ID NO:53, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:65, SEQ ID NO:69, SEQ ID NO:73, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:85, SEQ ID NO:89, SEQ ID NO:93, SEQ ID NO:298, SEQ ID NO:310, SEQ ID NO:322, SEQ ID NO:334, SEQ ID NO:346, or SEQ ID NO:358; and

(b) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:6, SEQ ID NO:14, SEQ ID NO:22, SEQ ID NO:26, SEQ ID NO:30, SEQ ID NO:34, SEQ ID NO:38, SEQ ID NO:42, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:54, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:66, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:86, SEQ ID NO:90, SEQ ID NO:94, SEQ ID NO:299, SEQ ID NO:311, SEQ ID NO:323, SEQ ID NO:335, SEQ ID NO:347, or SEQ ID NO:359.

7 . The method of claim 1 , wherein the heavy chain variable region and the light chain variable region are selected from the group consisting of:

(i) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:5, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:6;

(ii) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:13, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:14;

(iii) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:21, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:22;

(iv) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:25, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:26;

(v) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:29, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:30;

(vi) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:33, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:34;

(vii) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:37, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:38;

(viii) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:41, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:42;

(ix) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:45, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:46;

(x) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:49, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:50;

(xi) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:53, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:54;

(xii) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:57, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:58;

(xiii) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:61, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:62;

(xiv) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:65, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:66;

(xv) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:69, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:70;

(xvi) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:73, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:74;

(xvii) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:77, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:78;

(xviii) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:81, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:82;

(xix) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:85, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:86;

(xx) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:89, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:90;

(xxi) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:93, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:94;

(xxii) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:298, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:299;

(xxiii) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:310, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:311;

(xxiv) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:322, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:323;

(xxv) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to amino acids the sequence set forth in SEQ ID NO:334, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:335;

(xxvi) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:346, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:347; and

(xxvii) a heavy chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:358, and a light chain variable region comprising an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:359.

8 . The method of claim 1 , wherein:

(i) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:5, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:6;

(ii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:13, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:14;

(iii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:21, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:22;

(iv) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:25, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:26;

(v) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:29, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:30;

(vi) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:33, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:34;

(vii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:37, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:38;

(viii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:41, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:42;

(ix) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:45, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:46;

(x) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:49, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:50;

(xi) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:53, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:54;

(xii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:57, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:58;

(xiii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:61, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:62;

(xiv) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:65, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:66;

(xv) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:69, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:70;

(xvi) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:73, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:74;

(xvii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:77, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:78;

(xviii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:81, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:82;

(xix) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:85, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:86;

(xx) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:89, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:90;

(xxi) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:93, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:94;

(xxii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:298, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:299;

(xxiii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:310, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:311;

(xxix) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:322, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:323;

(xxv) the heavy chain variable region comprises amino acids the sequence set forth in SEQ ID NO:334, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:335;

(xxvi) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:346, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:347; or

(xxvii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:358, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:359.

9 . The method of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:65, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:66.

10 . The method of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:69, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:70.

11 . The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is fully human.

12 . The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is chimeric or humanized.

13 . The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is a Fab, a Fab′, a F(ab′)2, a variable fragment (Fv), or a single chain variable fragment (scFv).

14 . The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is a single chain variable fragment (scFv).

15 . The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises the amino acid sequence set forth in SEQ ID NO:101, SEQ ID NOS:103, SEQ ID NOS:105, SEQ ID NOS:106, SEQ ID NOS:107, SEQ ID NOS:108, SEQ ID NOS:109, SEQ ID NOS:110, SEQ ID NOS:111, SEQ ID NOS:112, SEQ ID NOS:113, SEQ ID NOS:114, SEQ ID NOS:115, SEQ ID NOS:116, SEQ ID NOS:117, SEQ ID NOS:118, SEQ ID NOS:119, SEQ ID NOS:120, SEQ ID NOS:121, SEQ ID NOS:122, SEQ ID NOS:123, SEQ ID NOS:300, SEQ ID NOS:312, SEQ ID NOS:324, SEQ ID NOS:336, SEQ ID NOS:348, or SEQ ID NOS:360.

16 . The method of claim 1 , wherein the cancer is multiple myeloma or Waldenstrom's macroglobulinemia.

17 . The method of claim 1 , wherein the cancer is multiple myeloma.

18 . The method of claim 2 , wherein the cancer is multiple myeloma.

19 . The method of claim 4 , wherein the cancer is multiple myeloma.

20 . The method of claim 5 , wherein the cancer is multiple myeloma.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 23, 2021

From: LIU, CHENG

To: EUREKA THERAPEUTICS, INC.

Reel/Frame 056023/0766 →

CONFIRMATORY PATENT ASSIGNMENT Recorded Apr 23, 2021

From: BRENTJENS, RENIER J.; SMITH, ERIC L.

To: MEMORIAL SLOAN-KETTERING CANCER CENTER

Reel/Frame 056032/0050 →